依托咪酯衍生物在GABA(A)受体上的构效关系：与11β-羟化酶结合的比较。

Structure-activity relationship of etomidate derivatives at the GABA(A) receptor: Comparison with binding to 11beta-hydroxylase.

作者信息

Atucha Erika, Hammerschmidt Friedrich, Zolle Ilse, Sieghart Werner, Berger Michael L

机构信息

Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University of Vienna, Austria.

出版信息

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4284-7. doi: 10.1016/j.bmcl.2009.05.065. Epub 2009 May 24.

DOI:10.1016/j.bmcl.2009.05.065

PMID:19497738

Abstract

At the GABA(A) receptor, low concentrations of etomidate potentiate the inhibitory effect of GABA on specific binding of the closed channel ligand [(3)H]ethynylpropylbicycloorthobenzoate ([(3)H]EBOB). Here, we present SARs for etomidate and structurally related compounds inducing this effect. In the absence of GABA, similar SARs, but 14-20 times weaker potencies were observed. We discuss these SARs in comparison to the much higher potencies of these compounds as inhibitors of 11beta-hydroxylase.

摘要

在GABA(A)受体上，低浓度的依托咪酯可增强GABA对封闭通道配体[(3)H]乙炔基丙基双环邻苯二甲酸酯([(3)H]EBOB)特异性结合的抑制作用。在此，我们展示了依托咪酯及诱导此效应的结构相关化合物的构效关系。在无GABA的情况下，观察到了类似的构效关系，但效力弱14 - 20倍。我们将这些构效关系与这些化合物作为11β - 羟化酶抑制剂时高得多的效力进行了比较。